Field of the Invention
The present invention relates to a drug and device combination, and, in particular, to a drug and device combination for administering an aerosolized medication to the lungs.
Description of the Related Art
Aerosol inhalation equipment such as nebulizers are often used in medical facilities for generating aerosol mists for diagnostic and therapeutic procedures. The mists can originate from liquids, suspensions, colloids, nano-colloids or nano- or micronized dry powders. Historically, these devices were solely used in hospitals but now some can be used in the home and include Metered Dose Inhalers (MDIs for patients with asthma or re-current bronchospasm.) Some patients with asthma, especially during severe episodes, do require nebulizer treatment at home but these devices are cumbersome and “continuous medication feed” therapy is not presently available in the home care setting.
Whether in the home or hospital, a metered dose is important because the therapeutic agents delivered (bronchodilators in asthma to congestive heart failure drugs such as VIP) are highly active biologically and dose must be controlled to impart precision and titration in the therapeutic or clinical effect seen especially when the patient is in home care setting. Such devices are especially useful, such as, for example, in pulmonary therapy for severe bronchospasm as in asthma, infectious diseases such as pneumonia (bacterial or fungal including Mycobacterium tuberculae), and vasodilators of the venous circulation systemically or within the pulmonary tree. They may be useful for introducing radioactive vapors or for special receptor binding agents used for diagnosing diseases. Typically, when devices have been developed for diagnostic use with radioactive materials, they are not used for therapeutic use because diagnostic devices require special handling, lead encasement for example, and a complex design compatible with safe uses of radioactive material. Diagnostic devices are typically designed for single application in hospitals or other medical facilities, where the use can be controlled. Diagnostic devices must prevent radioactive contamination to other caregivers and patients and in the physical area of treatment (room or corridor), and therefore route expelled air through a filter to prevent radioactive particles from exiting the device into the atmosphere. A key difference between diagnostic devices and drug delivery nebulizers is that the exhaled air path in drug delivery nebulizers is not controlled for drug delivery devices; while the purpose of controlling air flow in diagnostic radioactive agent delivery is to reduce contamination but not to optimize drug delivery. Another key difference is that residual volume can be higher than expected in diagnostic devices because the diagnostic devices are single use devices containing radioactive substances and therefore must be disposed immediately after use or within 30 minutes after the diagnostic procedure is complete, whereas drug delivery nebulizers can be reused.
To date, aerosol drug delivery has focused on pressurized cans or metered inhalers. Nebulizers used with an air pump have typically only been used for severe acute exacerbations of symptoms or where bronchospasm makes inspiration difficult. For conditions where expiration is reduced or restricted such as in asthma acutely and in chronic obstructive pulmonary disease (“COPD”) or emphysema, nebulizers are used acutely but over a longer period than one or two puffs used to relieve symptoms of asthma. In some cases, the nebulizers maybe used from minutes to hours until blood oxygen returns to normal and remains at normal levels. Especially in these cases where blood oxygen has fallen, the inhaled vapor should contain a “high payload of drug” per inspired breath to achieve the desired therapeutic effect. Delivering drugs under low-pressure conditions, by contrast, is difficult, patient pulmonary status dependent, and maybe ineffective. MDIs develop pressures up to 50 pounds per square inch upon exit at the nozzle (“psi”) to be effective and are in part dependent of the inhalation pressure or inspiration “vacuum” generated by the patient. Because inhalation pressure is low upon inhalation via a spacer for example and is dependent on the patient's lung capacity, parameters such as droplet size for aqueous and/or non-aqueous liquids and particle size for dry powders are very important to achieve a therapeutic effect. Furthermore, positive pressure MDIs effectively “blow” the medication into the nasopharynx with a high fraction of the dose adhering to the mucosal wall of the mouth and upper airway. Accordingly, the medication does not reach the lungs.
With the advent of resistant bacterial organisms, the improvements in treatment of diseases with high morbidity, such as idiopathic and or primary pulmonary hypertension, cystic fibrosis, persistent primary pulmonary hypertension, and systemic diseases such congestive heart failure with lung involvement, delivery of medications and/or drugs either as small molecules or proteins or peptides or polysaccharides or mucopolysaccharides is important. The aerosol drug delivery method offers advantages over the oral route of administration. Many highly effective agents such as those mentioned above cannot be given orally due to their acid labile properties; or because they are poorly tolerated when given by the intramuscular route. The intravenous route requires hospital care or attentive outpatient care and should be used only by nurses or those skilled or schooled. Pulmonary drug delivery is needed because it could be safe and effective if doses can be controlled and delivered properly.
The diseases where topical administration to the lung is associated with a more positive therapeutic outcome or therapeutic benefit include pneumonia, tuberculosis and cystic fibrosis where there is excessive mucous clogging the passages or bronchioles of the lung. For cystic fibrosis, where there is excess mucous clogging the airways or bronchioles of the lung, direct pulmonary treatment is the most effective therapy.
For aerosol drug delivery, therapies can be viewed simply and naively as topical therapy, but when droplet size is well-controlled and its distribution is homogenous, it can be improved to treat diseases requiring deep lung and/or alveolar targeted delivery. In the present case, deep lung delivery refers to penetration into the small airways of the lung typically ranging between 2-4 microns in diameter. For targeted alveolar drug delivery, droplets should be less than 2 microns, and preferably, less than about 1.1 microns but above 0.5 microns. In each case, the lung should be equally affected with no “dead” spots upon scanning or “clumping” in the larger bronchioles. The device ideally should deliver an even intra-pulmonary distribution of the medication.
For aerosol drug delivery, especially for deep lung or targeted alveoladelivery, it would be beneficial to provide a multi-use, refillable, and re-useable portable aerosol inhalation device that targets the deep lung and alveolar surfaces and that can be used outside of a medical facility, at home or under supervision in a chronic care facility, such as a nursing home. Further, the device should filter the exhaled air and have low residual volumes to prevent contamination or inadvertent exposure, especially with antibiotics, since many people and caregivers have circulating antibodies and can experience an allergic reaction to such chemicals; typically this is seen with penicillin. Still further, the device should have unique ports for placing the medication into an aerosolizing chamber, with minimal loss or inadvertent exposure, more than once and for the device to allow disassembling for cleaning when required and re-use.